细胞核内小干扰RNA介导的表观遗传和基因表达调控

Small-interfering RNA-mediated epigenetics and gene regulation in the nucleus

RNA干扰(RNAi)是真核生物中一个非常广泛而且保守的基因表达调节机制.长度为20~30个核苷酸的具有调控作用的小RNA广泛存在于几乎所有的真核细胞中,这些小RNA参与和调控许多基本的生命过程,如异染色质的形成、基因组稳定性的维持、发育的时空调节、细胞命运的决定、DNA的损伤与修复反应,以及抗病毒反应等.这些小RNA的产生和调节的失衡往往会导致一系列重大疾病的发生与发展.RNAi在细胞质里主要是通过抑制翻译和诱导靶标mRNA的降解来进行.在细胞核中,RNAi则有多种作用方式.本文将重点阐述小RNA在细胞核里的基因表达调控的分子机制,包括诱导异染色质形成、介导表观遗传修饰、调控染色体分离,以及调控转录和选择性剪切等过程.

RNA interference （RNAi） is a widely conserved gene regulation mechanism in eukaryotes. Small regulatory RNAs （20-30 nt in length） are widely present in nearly all eukaryote cells. These small regulatory RNAs are engaged in many essential biological processes, including but not limited to heterochromatin formation, maintenance of genome integrity, spatiotemporal developmental regulation, cell fate decisions, DNA repair, and antiviral reactions. Dysregulation of the biogenesis and homeostasis of these small regulatory RNAs can often lead to a variety of severe human diseases. In the cytoplasm, RNAi usually act through inhibiting protein translation or inducing mRNA degradation. In the nucleus, RNAi can act via a number of mechanisms. In this review, we will focus on the mechanisms of small RNA-mediated gene regulation in the nucleus, including heterochromatin formation, epigenetic modification, chromosome segregation, transcriptional regulation, and alternative splicing.